{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:29:58Z","timestamp":1780082998538,"version":"3.54.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>\n                    Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the CNS, characterized by neuroinflammatory, axonal degeneration, and pronounced sexual dimorphism. Experimental data implicate dysregulated 5-HT levels in MS. However, the effects of clinical parameters and disease-modifying-therapies (DMTs) on peripheral 5-HT concentrations remain underexplored. This study aimed to quantify peripheral levels of tryptophan (Trp), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) in patients with relapsing\u2013remitting MS (RRMS) and to assess the effects of BMI, DMT duration, and specific DMT regimens. In this cross-sectional analysis, 226 participants were enrolled and stratified into four groups: healthy men (HM;\n                    <jats:italic>n<\/jats:italic>\n                    \u202f=\u202f29), healthy women (HW;\n                    <jats:italic>n<\/jats:italic>\n                    \u202f=\u202f84), men with RRMS (MMS;\n                    <jats:italic>n<\/jats:italic>\n                    \u202f=\u202f29), and women with RRMS (WMS;\n                    <jats:italic>n<\/jats:italic>\n                    \u202f=\u202f84). Serum concentrations of Trp, 5-HT, and 5-HIAA were measured using reverse-phase high-performance liquid chromatography (HPLC) with fluorescence detection. Nonparametric statistical tests were applied. Peripheral 5-HT levels were significantly reduced in underweight WMS (BMI\u202f&amp;lt;\u202f18\u202fkg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ;\n                    <jats:italic>p<\/jats:italic>\n                    \u202f&amp;lt;\u202f0.05), WMS with DMT duration over 4\u202fyears (\n                    <jats:italic>p<\/jats:italic>\n                    \u202f&amp;lt;\u202f0.01), and WMS receiving interferon beta-1a (\n                    <jats:italic>p<\/jats:italic>\n                    \u202f&amp;lt;\u202f0.01) compared to HW. No significant intergroup differences in Trp or 5-HIAA were observed across all stratifications. These findings reveal a novel association between reduced peripheral 5-HT and specific clinical-therapeutic factors in WMS, extending recent MS research on sex-specific vulnerabilities, serotonergic dysregulation in neuroinflammation, and psychiatric comorbidity. By highlighting the influence of low BMI, prolonged DMT exposure, and interferon beta-1a on 5-HT homeostasis, this study underscores the need for multidisciplinary management integrating neurological and psychiatric care in WMS and suggests avenues for precision interventions targeting serotonergic pathways to reduce disease burden.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2026.1752975","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:37:44Z","timestamp":1773207464000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced peripheral serotonin levels in women with multiple sclerosis: associations with underweight status, treatment duration, and use of interferon beta 1a"],"prefix":"10.3389","volume":"20","author":[{"given":"Gilberto","family":"P\u00e9rez-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Laboratorio de Psicoinmunolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le\u00f3n Arturo","family":"Aguilar-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Laboratorio de Psicoinmunolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle Berenice","family":"Vela-Sancho","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda Molecular, Instituto de Neurociencias Translacionales, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara","place":["Guadalajara, Jalisco, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salom\u00f3n","family":"Jacinto-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Laboratorio de Psicoinmunolog\u00eda, Instituto 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Polit\u00e9cnico Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Paulina","family":"Reyes-Mata","sequence":"additional","affiliation":[{"name":"Departamento de Disciplinas filos\u00f3fico, Metodol\u00f3gicas e Instrumentales, CUCS, Universidad de Guadalajara","place":["Guadalajara, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Alberto","family":"Mireles-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades (HE), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS)","place":["Guadalajara, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 de Jes\u00fas","family":"Guerrero-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Banco Central de Sangre, Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades (HE), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano de Seguro Social (IMSS)","place":["Guadalajara, Jalisco, Mexico"]},{"name":"Departamento de Farmacobiolog\u00eda, Centro Universitario de Ciencias Exactas e Ingenier\u00edas (CUCEI), Universidad de Guadalajara","place":["Guadalajara, Jalisco, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ortu\u00f1o-Sahag\u00fan","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda Molecular, Instituto de Neurociencias Translacionales, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara","place":["Guadalajara, Jalisco, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenin","family":"Pav\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Psicoinmunolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz","place":["Ciudad de M\u00e9xico, 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Neurol."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2026.1752975\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:37:45Z","timestamp":1773207465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2026.1752975\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":34,"alternative-id":["10.3389\/fncel.2026.1752975"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2026.1752975","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"article-number":"1752975"}}